Two-photon fluorescence sensors for imaging NMDA receptors and monitoring release of Zn²⁺ from the presynaptic terminal

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>Synaptic Zn<SUP>2+</SUP> plays an important role in neurotransmission and a neuromodulator. The development of the imaging tools for monitoring spatiotemporal changes taking place in synaptic Zn<SUP>2+</SUP> concentrations is necessary in order to understand the role of Zn<SUP>2+</SUP> in the function of many aspects of the glutamate system. In this work, two-photon probes <B>1</B> and <B>2</B>, bearing ifenprodil-like tails that have affinity for NMDA receptors of neuronal cells, were designed and prepared. The two-photon fluorescent probe <B>1</B>, which bears (N-(6-acetylnaphthalen-2-yl)-N-methylglycine) as two-photon fluorophore, enables high resolution imaging of neuronal cells. The two-photon fluorescent probe <B>2</B>, which contains the di-2-picolylamine (DPA) as a Zn<SUP>2+</SUP>-binding site, the naphthalimide unit as the two-photon fluorophore, and the ifenprodil-like tail as the NMDA receptor binding moiety, can be employed for selective detection of Zn<SUP>2+</SUP> located near the NMDA receptor and for monitoring concentration changes of Zn<SUP>2+</SUP> in live neurons and hippocampal tissues.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Two-photon probes <B>1</B> and <B>2</B>, bearing ifenprodil-like tails that have affinity for NMDA receptors of neuronal cells, were designed and synthesized. </LI> <LI> Probe <B>1</B> can be used to image NMDA receptors in neuronal cells with two-photon microscopy. </LI> <LI> Probe <B>2</B> was able to sensitively monitor Zn<SUP>2+</SUP> located near NMDA receptors. </LI> <LI> Probe <B>1</B> and <B>2</B> can be successfully applied to image NMDA receptors in hippocampal tissues for two-photon fluorescence imaging. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>